Impact of FMS-like tyrosine kinase 3 inhibitor maintenance on post-transplant outcomes in acute myeloid leukemia with FMS-like tyrosine kinase 3 mutations: a real-world German registry analysis highlighting sorafenib

FLT3-mutation occurs in 25-30% of acute myeloid leukemia (AML) and confers high relapse risk and inferior survival. Allogeneic hematopoietic cell transplantation (allo-HCT) offers curative potential, yet relapse remains a major post-transplant challenge. Maintenance therapy with FLT3 inhibitors (FLT3i) after allo-HCT has emerged as a promising strategy, but real-world evidence remains limited. This study aimed to assess the impact of FLT3i maintenance on transplant outcomes. We analyzed 523 adults with FLT3-internal tandem duplications (ITD) AML in first complete remission who underwent allo-HCT between 2011 and 2023 in 13 German transplant centers participating in the national German Registry for Hemato-poietic Stem Cell Transplantation and Cell Therapy registry; 22% received FLT3i maintenance (sorafenib 49%, midostaurin 37%, gilteritinib 5%, unknown 9%). In multivariable analyses, FLT3i maintenance improved overall survival (OS) (hazard ratio [HR]=2.25; 95% confidence interval [CI]: 1.28-3.95; P=0.005), relapse-free survival (RFS) (HR=1.72; 95% CI: 1.05-2.81; P=0.030), non-relapse mortality (HR=3.62, 95% CI: 1.08-12.11; P=0.037), and graft-versus-host disease-free, relapse-free survival (GRFS) (HR=1.59; 95% CI: 1.06-2.40; P=0.025). The cumulative incidence of relapse did not differ. In univariate analyses (UVA), OS benefits were observed in MRD-positive (HR=2.35; 95% CI: 1.04-5.31; P=0.025) and MRD-negative patients (HR=2.64; 95% CI: 1.05-6.68; P=0.020. Sorafenib maintenance (N=50) demonstrated superior efficacy with 5-year OS of 85% versus 62% (HR=2.979; P=0.0045) and RFS of 84% versus 55% (HR=2.771; P=0.0043) compared to no maintenance. These real-world findings, while limited by the retrospective design and potential selection bias, align with randomized trial data and support the use of FLT3i maintenance as part of post-transplant care for FLT3. ©2026 Ferrata Storti Foundation Published under a CC BY-NC license